Trial Outcomes & Findings for Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C (NCT NCT01121185)

NCT ID: NCT01121185

Last Updated: 2016-06-14

Results Overview

Serum HCV RNA was measured by Quantitative RT-PCR

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

At Day 42 post-transplantation

Results posted on

2016-06-14

Participant Flow

Patients with HCV genotype 1a infection scheduled to undergo liver transplantation were recruited at 8 U.S. transplantation centers between June 2010 and April 2011. Due to slower than anticipated subject accrual, enrollment was stopped after 13 subjects were randomized; 11 underwent liver transplantation and received the study intervention.

Reasons for exclusion after randomization included identification of a protocol-specified exclusion criterion in the recipient or the donor at the time of organ offer or failure to undergo liver transplantation.

Participant milestones

Participant milestones
Measure	Experimental: MBL-HCV1 Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Overall Study STARTED	7	6
Overall Study Infused	7	5
Overall Study Transplanted	6	5
Overall Study COMPLETED	6	5
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Experimental: MBL-HCV1 Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Overall Study Not infused	0	1
Overall Study Not transplanted	1	0

Baseline Characteristics

Study in Hepatitis C Virus (HCV) Infected Patients Undergoing Liver Transplantation to Evaluate a Human Monoclonal Antibody Against Hepatitis C

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Total n=11 Participants Total of all reporting groups
Age, Continuous	60.9 years n=5 Participants	57.2 years n=7 Participants	59.2 years n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	5 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Hepatocellular carcinoma	4 participants n=5 Participants	2 participants n=7 Participants	6 participants n=5 Participants
Serum HCV RNA concentration	6.07 log10 IU/mL n=5 Participants	5.59 log10 IU/mL n=7 Participants	6.03 log10 IU/mL n=5 Participants

PRIMARY outcome

Timeframe: At Day 42 post-transplantation

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Serum HCV RNA was measured by Quantitative RT-PCR

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Proportion of Subjects With Detectable Serum HCV RNA at Day 42 Post-Transplantation	100 percentage of participants	100 percentage of participants

SECONDARY outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Adverse events were assessed by targeted medical history, physical examinations and laboratory testing. Subjects were asked at scheduled study visits through day 42 whether they experienced solicited adverse reactions (fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives). In addition to these solicited adverse events, subjects were asked at all scheduled study visits through day 56 to report any other adverse events, regardless of whether the event was thought to be related to the study infusions. Adverse events were summarized by System Organ Class (SOC) using MedDRA (version 12.0)

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation General Disorders And Administration Site Conditio	13 events	6 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Gastrointestinal Disorders	9 events	9 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Metabolism And Nutrition Disorders	7 events	10 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Investigations	16 events	7 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Nervous System Disorders	7 events	3 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Skin And Subcutaneous Tissue Disorders	3 events	4 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Injury, Poisoning And Procedural Complications	4 events	3 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Respiratory, Thoracic And Mediastinal Disorders	3 events	2 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Renal And Urinary Disorders	4 events	1 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Psychiatric Disorders	3 events	1 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Vascular Disorders	2 events	1 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Blood And Lymphatic System Disorders	1 events	2 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Infections And Infestations	1 events	9 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Eye Disorders	1 events	1 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Musculoskeletal And Connective Tissue Disorders	2 events	1 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Hepatobiliary Disorders	1 events	0 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Reproductive System And Breast Disorders	1 events	0 events
The Incidence of Adverse Events and Treatment-Emergent Adverse Events Determined Through Medical History, Physical Examination and Laboratory Evaluation Ear And Labyrinth Disorders	0 events	1 events

SECONDARY outcome

Timeframe: Baseline and Day 3, 14, 28 and 42 Post-Transplantation

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Serum HCV RNA was measured by quantitative RT-PCR. The change in HCV RNA from baseline was obtained by calculating the difference between the baseline pre-transplantation HCV RNA level and the HCV RNA level measured at each study visit.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation Day 3	-3.07 log10 IU/mL Interval -3.45 to -2.17	-1.01 log10 IU/mL Interval -2.87 to 1.03
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation Day 14	-2.48 log10 IU/mL Interval -3.77 to 0.81	0.10 log10 IU/mL Interval -2.6 to 2.09
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation Day 28	-0.75 log10 IU/mL Interval -3.23 to 1.01	1.22 log10 IU/mL Interval -2.0 to 2.59
Change in Serum HCV RNA Between Baseline and Day 3, 14, 28 and 42 Post-Transplantation Day 42	0.23 log10 IU/mL Interval -1.16 to 0.93	1.22 log10 IU/mL Interval -2.14 to 2.72

SECONDARY outcome

Timeframe: Baseline Day 0 and Day 42

Population: The 11 subjects who were randomized, initiated study infusions, and underwent transplantation were included in the analysis population. On day 0, all subjects had pre-transplant biopsy specimens available for analysis. On day 42, 4 subjects in the MBL-HCV1 group and 5 subjects in the placebo group had biopsy specimens available for analysis.

Liver biopsies obtained at baseline (day 0) and day 42 post-transplantation were assessed for histologic evidence of hepatitis by a pathologist blinded to treatment assignment using the Ishak modification of the Knodell histologic grading system to assign a histologic activity index (HAI) score. The HAI score consists of a sum of four components: 1) periportal or periseptal interface hepatitis; 2) confluent necrosis; 3) focal lytic necrosis, apoptosis and focal inflammation; 4) portal inflammation. The total HAI score can range from a minimum of 0 to a maximum of 18, with higher scores indicating more severe hepatic inflammation.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 Day 0	0.0 Histologic activity index (HAI) score Interval 0.0 to 0.0	1.0 Histologic activity index (HAI) score Interval 0.0 to 2.0
Histologic Evidence of Hepatitis by Histologic Activity Index (HAI) Score at Baseline and Day 42 Day 42	0.6 Histologic activity index (HAI) score Interval 0.0 to 1.0	4.0 Histologic activity index (HAI) score Interval 1.0 to 6.0

SECONDARY outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Biochemical function was assessed by measurement of alanine aminotransferase (ALT) and total bilirubin and synthetic function was assessment by measurement of the pro-thrombin time (reported as the international normalized ratio, INR) at multiple time-points during the 56-day study period. The table below displays the INR at each time-point. The INR is the ratio of a patient's prothrombin time to a control sample, raised to the power of the ISI value (International Sensitivity Index) for the batch of tissue factor being used for the assay.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 0	1.6 unitless Interval 1.1 to 2.7	1.5 unitless Interval 1.0 to 2.9
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 1	1.4 unitless Interval 1.1 to 1.6	1.3 unitless Interval 1.1 to 1.6
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Screening	1.5 unitless Interval 1.0 to 2.3	1.5 unitless Interval 0.97 to 2.9
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 2	1.2 unitless Interval 1.0 to 1.4	1.3 unitless Interval 1.0 to 1.6
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 3	1.2 unitless Interval 0.9 to 1.6	1.1 unitless Interval 1.0 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 4	1.5 unitless Interval 0.9 to 3.3	1.1 unitless Interval 1.0 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 5	1.6 unitless Interval 0.9 to 4.0	1.1 unitless Interval 1.1 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 6	1.4 unitless Interval 0.9 to 2.7	1.2 unitless Interval 1.05 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 7	1.3 unitless Interval 1.0 to 2.2	1.1 unitless Interval 0.99 to 1.3
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 14	1.2 unitless Interval 1.0 to 1.7	1.1 unitless Interval 0.95 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 21	2 unitless Interval 1.1 to 3.7	1.1 unitless Interval 0.96 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 28	1.6 unitless Interval 1.0 to 3.0	1.1 unitless Interval 0.93 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 42	1.2 unitless Interval 1.0 to 1.6	1.1 unitless Interval 0.98 to 1.2
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / International Normalized Ratio (INR) Day 56	1.1 unitless Interval 1.0 to 1.2	1.1 unitless Interval 1.0 to 1.3

SECONDARY outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Screening	74 U/L Interval 46.0 to 107.0	114 U/L Interval 60.0 to 263.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 0	76 U/L Interval 44.0 to 111.0	107 U/L Interval 71.0 to 164.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 1	565 U/L Interval 90.0 to 1571.0	404 U/L Interval 88.0 to 832.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 2	501 U/L Interval 75.0 to 1084.0	415 U/L Interval 87.0 to 986.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 3	374 U/L Interval 62.0 to 799.0	464 U/L Interval 80.0 to 1385.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 4	301 U/L Interval 56.0 to 572.0	355 U/L Interval 57.0 to 975.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 5	243 U/L Interval 57.0 to 421.0	253 U/L Interval 49.0 to 626.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 6	207 U/L Interval 50.0 to 295.0	219 U/L Interval 43.0 to 495.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 7	163 U/L Interval 48.0 to 208.0	176 U/L Interval 37.0 to 338.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 14	38 U/L Interval 15.0 to 77.0	54 U/L Interval 21.0 to 116.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 21	34 U/L Interval 13.0 to 60.0	55 U/L Interval 15.0 to 141.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 28	21 U/L Interval 7.0 to 26.0	109 U/L Interval 18.0 to 232.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 42	22 U/L Interval 14.0 to 32.0	174 U/L Interval 14.0 to 426.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Alanine Aminotransferase (ALT) Day 56	41 U/L Interval 23.0 to 96.0	183 U/L Interval 19.0 to 606.0

SECONDARY outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Screening	2.8 mg/dL Interval 1.2 to 5.0	8.9 mg/dL Interval 0.57 to 33.7
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 0	2.6 mg/dL Interval 0.8 to 4.1	2.9 mg/dL Interval 0.64 to 5.5
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 1	3.3 mg/dL Interval 0.8 to 6.1	4.7 mg/dL Interval 2.07 to 10.1
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 2	2.3 mg/dL Interval 1.1 to 3.1	4.1 mg/dL Interval 1.76 to 8.7
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 3	2 mg/dL Interval 1.2 to 3.1	4.7 mg/dL Interval 1.72 to 9.1
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 4	2 mg/dL Interval 1.4 to 2.8	5.5 mg/dL Interval 1.44 to 10.9
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 5	2.1 mg/dL Interval 1.3 to 3.6	7 mg/dL Interval 1.47 to 12.5
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 6	2.6 mg/dL Interval 1.3 to 5.1	8.3 mg/dL Interval 1.22 to 17.1
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 7	3 mg/dL Interval 1.0 to 9.2	8.2 mg/dL Interval 1.11 to 19.0
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 14	1.2 mg/dL Interval 0.7 to 2.7	2.6 mg/dL Interval 0.49 to 4.9
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 21	1 mg/dL Interval 0.6 to 2.0	1.7 mg/dL Interval 0.37 to 2.8
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 28	0.9 mg/dL Interval 0.5 to 1.4	1.5 mg/dL Interval 0.27 to 2.4
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 42	0.8 mg/dL Interval 0.5 to 1.1	1.2 mg/dL Interval 0.29 to 1.9
Graft Function Assessed by Measurement of Biochemical and Synthetic Function at Multiple Time Points / Total Bilirubin Day 56	0.7 mg/dL Interval 0.4 to 0.9	2 mg/dL Interval 0.16 to 5.3

SECONDARY outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

Serum HCV RNA was measured by Quantitative RT-PCR

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Time to Onset of Recurrence of Detectable HCV RNA Post-Transplantation	NA days The planned analysis could not be performed because an insufficient number of participants had undetectable HCV RNA post-transplantation. A post-hoc analysis of time to virologic rebound (≥ 1 log10 increase above viral nadir) was performed.	NA days The planned analysis could not be performed because an insufficient number of participants had undetectable HCV RNA post-transplantation. A post-hoc analysis of time to virologic rebound (≥ 1 log10 increase above viral nadir) was performed.

POST_HOC outcome

Timeframe: Through Day 56

Population: The eleven subjects who were randomized, initiated study infusions, and underwent liver transplantation were included in the analysis population.

The time of viral rebound was defined as the time of the first measurement of serum HCV RNA increased ≥ 1 log10 from the viral nadir (the lowest serum HCV RNA level post-transplantation). Serum HCV RNA was measured by RT-PCR.

Outcome measures

Outcome measures
Measure	Experimental: MBL-HCV1 n=6 Participants Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 Participants Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
Time To Viral Rebound Post-Transplantation(Serum HCV RNA Increased ≥ 1 log10 From Viral Nadir)	22.7 days Interval 15.0 to 34.4	2.33 days Interval 1.18 to 3.1

Adverse Events

Experimental: MBL-HCV1

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo Comparator: 0.9% Sodium Chloride

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental: MBL-HCV1 n=6 participants at risk Eleven intravenous infusions of MBL-HCV1 (50 mg/kg) human monoclonal antibody administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.	Placebo Comparator: 0.9% Sodium Chloride n=5 participants at risk Eleven intravenous infusions of 0.9% sodium chloride administered during the first 14 days post-transplantation: three infusions were given on Day 0 (1-4 hours prior to anhepatic phase, during the anhepatic phase, and within 4-12 hours post-reperfusion), daily infusions were administered on days 1 through 7, and the final infusion was given on day 14 ± 2 post transplantation.
General disorders Chest Pain	16.7% 1/6 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	0.00% 0/5 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Gastrointestinal disorders Vomiting	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Infections and infestations Clostridium Difficile Colitis	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Infections and infestations Hepatitis C	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	40.0% 2/5 • Number of events 2 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Injury, poisoning and procedural complications Post Procedural Haemorrhage	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Investigations Blood Creatinine Increased	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Investigations Blood Glucose Fluctuation	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Investigations Liver Function Test Abnormal	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.
Metabolism and nutrition disorders Failure To Thrive	0.00% 0/6 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.	20.0% 1/5 • Number of events 1 • Adverse events were assessed from the start of the first infusion through day 56 post-transplantation Adverse events were assessed by history, physical examinations and laboratory testing through day 56. In addition, the following adverse reactions were specifically solicited through day 42: fever, chills, nausea, rash, joint pain or swelling, shortness of breath, headache, fatigue, and hives.

Other adverse events

Additional Information

Director Clinical Affairs

MassBiologics

Phone: 617-474-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
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Restriction type: LTE60